Application of radiotherapy-preexcited gambogic acid dual targeting nanoparticles in colorectal cancer

Delivering anti-tumor drugs to the correct location is an important strategy for improving tumor treatment efficacy and reducing side effects. To this end, this study developed a P-selectin-targeted drug delivery platform, where fucoidan-modified PLGA nanoparticles were loaded with the anti-tumor drug gambogic acid (GA) to form a novel nanoparticle, Fucoidan-PLGA/GA NPs (FPG). Fucoidan serves as a natural hydrophilic shell, enabling specific dual-targeting by binding to P-selectin overexpressed on tumor vascular endothelial cells and tumor cells, allowing FPG to cross the vascular barrier and reach the tumor tissue. In vitro and in vivo experimental results demonstrate that FPG has excellent binding capability to tumor cells and endothelial cells. The radiation-induced differential expression of P-selectin further enhances drug-targeted delivery. FPG combined with radiotherapy exhibited significant advantages in inhibiting tumor growth, inducing apoptosis, reducing tumor volume, modulating the immune microenvironment, and promoting cell phagocytosis. This targeted delivery system holds great potential for improving tumor treatment efficacy and reducing side effects in future cancer therapies.